The objective of the proposed experiments is to provide morphological and correlated biochemical information on the alterations which occur in rat hepatocytes made diabetic by streptozotocin administration. The hypothesis is presented that the diabetic state may reflect in part an effect on hepatocyte morphology and microsomal membrane composition. Hepatocytes from diabetic animals exhibit an increase in amount of smooth endoplasmic reticulum and microsomal glucose-6-phosphatase (G-6-Pase) specific activity per mg membrane protein. The time dependent nature of this response for each of the microsomal elements (rough and smooth endoplasmic reticulum and Golgi apparatus) will be used to monitor for alterations in these microsomal components. G-6-Pase is a key rate controlling enzyme in gluconeogenesis; thus its microsomal location makes it a notable enzyme to investigate in this study of the morphology and biochemistry of the diabetic state. The results of these experiments will be analyzed in the light of studies which will compare the rates of membrane biogenesis in SER, RER, and Golgi apparatus in normal and diabetic liver. Insulin effects on the hepatocyte will be determined by administering sufficient insulin to prevent the onset of streptozotocin mediated diabetes. The ultrastructural and biochemical response to this treatment will then be followed. To control for streptozotocin effects other than those mediating the onset of diabetes, the streptzotocin effect at the level of the pancreatic beta cells will be allowed to take place in the presence of insulin. Insulin will then be withdrawn after appropriate times and the effect of the controlled removal of insulin with resultant onset of diabetes on hepatocyte ultrastructure and biochemistry determined.